Improving Syrian refugees’ knowledge of medications and adherence following a randomized control trial assessing the effect of a medication management review service

Background Syrian refugees living in Jordan have many chronic conditions and use many medications. Pharmacists delivering the Medication Management Review (MMR) service can have a role in improving this growing global refugees’ problem. Objectives To assess the effect of the MMR service on adherence to treatment therapy and knowledge of chronic medications for Syrian refugees residing in Jordan. Methods This randomized intervention control single-blinded study was conducted in Jordan. Syrian refugees were recruited and randomized into intervention and control groups. Two home visits were delivered to each participant, at baseline and three months later. All participants completed questionnaires regarding adherence and knowledge. As a part of the MMR service, treatment-related problems (TRPs) were recognized for all patients; recommendations to resolve these TRPs were only delivered to intervention group refugees’ physicians; TRPs were corrected. At follow-up, TRPs assessment, adherence and medication knowledge were assessed for all refugee participants. Results Participants (n = 106; intervention n = 53, control n = 53) had a number of medications and diagnosed chronic diseases of 5.8 ± 2.1 and 2.97 ± 1.16 per participant respectively. A significant improvement in the adherence and knowledge scores were noted in the intervention (P < 0.001 for both) but not the control group (P = 0.229, P = 0.07 respectively). Conclusion The MMR service can significantly improve refugees’ TRPs, adherence to therapy and knowledge of chronic medications. If this approach was extended to the large scale, many refugees in need would be able to access a quality essential health-care service; a step towards achieving universal health coverage. Trial registration Registry: ClinicalTrials.gov Identifier: NCT04554810.

The United Nations reported that, as of February 2016, a total of 13.5 million Syrian refugees 89 had been identified as in need of humanitarian aid; of these refugees, 6.6 million were 90 displaced within Syria and 4.8 million outside of Syria [1]. Refugees in general experience 91 low living conditions, limited access to health care services as well as high poverty level in the 92 country of settlement [1]. Taking these factors into consideration, refugees often have multiple 93 health issues that need extensive health care [1][2][3][4][5][6]. In this context, low adherence to treatment 94 and poor knowledge of medications and therapeutic regimens can be expected. Adherence to 95 treatment can be an issue to many refugees, as getting their medications on time, and being 96 provided with enough education on the importance of taking their medications as prescribed 97 can be lacking [7,8]. Medication knowledge has been defined as 'the awareness of the drug 98 name, purpose, administration schedule, adverse effects or side-effects, or special 99 administration instructions' [9]. It has been found that patients who need to take various  The primary aim of this study was to assess refugees' adherence and knowledge of their chronic   Inclusion criteria for the Syrian refugees included ≥ 18 years, living in Jordan for more than 135 six months prior to study recruitment and intending to stay for the whole study period, having 136 one chronic condition at least or taking 5 or more medications or taking more than 12 doses of 137 a medication per day [18]. There was a deviation from the original study protocol regarding the 138 sample size, as the calculated needed number of patients was 138 patients, however the 139 recruited number was 109, due to time restriction.

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An informed consent form was signed by all participants who accepted to participate. Eligible 141 participants were then randomized into intervention and control groups using a predetermined 142 list obtained by the computer randomization program (www.randomizer.org) before starting 143 the study. The study was singleblinded, hence, participants were not informed of the group 144 they were randomized into, but they were informed that they would have been in either of two 145 study groups. The first group would have received the MMR service during the study period, 146 while the to the other group directly after the study was completed (after three months' time).

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After the eligible patients were randomized into two groups, intervention group and control 149 group, appointments were arranged at the physicians' clinics for all participants to be visited  The MMR service was completed following verification of collected baseline data. The home 156 visits were planned not to exceed one hour, which is the usual time provided in related studies The clinical pharmacist identified and documented the treatment-related problems (TRPs) for 160 each patient in both groups at baseline. All identified TRPs were supported by current 161 therapeutic guidelines, reported in a letter format sent to the participant's physician. In the case 162 any life-threatening TRPs were identified for control groups participants, they were excluded 163 from the study for ethical considerations.   were detected using paired sample t-test for continuous variables. Group differences (between 210 the intervention and control groups) were detected using the independent sample t-test or Mann 211 Whitney U-test (based on the normality of data following testing) for continuous variables.

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Categorical data were expressed as proportion (%) and analysed using Chi-square test. A 213 probability value of < 0.05 was considered to be statistically significant for all analysis's tests.

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A total of 123 Syrian refugee participants were approached for recruitment into the study. After 224 participants' first meeting during the home visit by the clinical pharmacist, 116 participants 225 (94.3%) were found eligible for study and 10 participants refused to continue in the study due 226 to different causes ( Figure 1). Participants (n=109) were randomized into intervention (n=55) 227 and control (n=54) groups thereafter. The acceptance rate for home visits was 100%. No 228 participants with life-threatening cases were identified in the control group.

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Adherence to medications at baseline and follow-up 237 A significant improvement in the adherence scores was noted in the active group across the 238 study (P < 0.001, paired sample t-test). No significant improvement was found in the control 239 group regarding the mean change in the adherence score ( Figure 2).  There was no significant difference with regards to patients' commitment to pharmacist advice 247 between the two groups at baseline; at follow-up, a significant difference was found (P = 0.01,

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Chi-square test). Around 73% of intervention group patients were committed to the pharmacist 249 advice at baseline compared to 88% commitment at follow-up.

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Causes of non-adherence to medications were assessed at baseline visits. More than one third 251 of the patients in the intervention group and the control group reported that the price was the 252 main cause for non-adherence to their medication (39.7% and 37.7% respectively). Other 253 causes for patients' non-adherence are listed in table (2). There was no statically significant 254 difference between the two groups regarding the reported causes for non-adherence to 255 medications at baseline (P= 0.764, Chi-square test).

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Regarding the degree of patients' commitment to pharmacist advice, there was no significant 257 difference between the two groups at baseline. At follow-up, a significant improvement was 258 found in the intervention group but not the control group. (P = 0.01, Chi-square test) ( Table 3).

Knowledge of medications at baseline and follow-up 260
At baseline, no significant difference was found between the intervention and the control 261 groups with regards to 'Knowledge about medications mean scores (P 0.499, Independent 262 sample t-test). At follow-up, the difference was significant between the two groups (P < 0.001,

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Independent sample t-test). Across the study, there was a significant difference within the 264 intervention group, but not the control group (Figure 3).

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Upon comparison between the intervention and the control groups regarding the five domains 266 included in the 'knowledge about drug therapy' questionnaire, there was no significant 267 difference between the two groups in the five domains at baseline. However, significant 268 differences resulted at follow-up regarding all domains (Table 4).

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The current study showed that the provision of the pharmacist-lead MMR service can lead to   In particular, delivery of MMR services to refuges would contribute to achieve the SGD targets Employment and Economic Growth [37] calling for "ambitious solutions to ensure that the 335 world has the right number of jobs for health workers with the right skills and in the right places 336 to deliver universal health coverage". A focus on trained universal health-workforce that has 337 the ability to deliver different healthcare services in humanitarian settings was highlighted [37].     Table 1